Benzo[a]pyrene (BP), a ubiquitous carcinogen found in tobacco smoke, burning fossil fuels and animal and human diets, forms BP diol epoxide (BPDE)-DNA adducts in animals and humans sufficiently exposed. However, human BPDE-DNA adduct levels would most likely be low and beyond the sensitivity of routine radioimmunoassay and chromatographic analysis. Therefore, enzyme-linked immunosorbent assay (ELISA), ultrasensitive enzymatic radioimmunoassay (USERIA), and synchronous fluorescence spectrophotometry (SFS) have been employed to study these markers in subpopulations in humans with cancer who are considered at high risk for cancer, due in part to BP exposure. With these assays, putative BPDE-DNA adducts have been detected and quantitated in DNA isolated from peripheral blood lymphocytes (PBLs) of several aspshalt workers (roofers), foundry workers (coke oven), and head and neck, and lung cancer patients; in DNA from lung tissue, bronchial washings, and areolar macrophages of some lung cancer patients; and smoking and nonsmoking, occupationally unexposed, normal volunteers. Antibodies to BPDE-DNA adducts were also found in sera from highly exposed coke oven workers. These data support the conclusion that the activation of BP to its ultimate carcinogen and the subsequent adduction of the metabolite to DNA occurs in humans. Preliminary evidence indicates that other polycyclic aromatic hydrocarbons (i.e., chrysense and benzo[a]anthracene-DNA adducts) may also induce immune responses in humans.